title: Successful treatment of stem cell graft failure in pediatric patients using a submyeloablative regimen of campath-1H and fludarabine.
abstract: Graft failure is a significant cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). We used a nonmyeloablative conditioning regimen consisting of the lympho-depleting humanized CD52-antibody Campath-1H and fludarabine to rescue 12 consecutive children age 9 months to 17 years with engraftment failure after initial myeloablative HSCT. Primary diagnoses included lymphohematologic malignancies (n=6), severe combined immunodeficiency syndrome (SCID) (n=4), and metabolic diseases (n=2). The same stem cell donor was used as for the primary graft: mismatched family member (n=7), matched unrelated donor (n=4), or matched related donor (n=1). The patients received doses of CD34+ cells that did not significantly differ from those used in the initial, failed transplant. At a median follow-up of 51 months (range, 4 to 84 months), 6 of 6 patients with nonmalignant diseases and 4 of 6 patients with malignancy were alive. Two patients died, 1 patient from pulmonary toxicity and 1 from relapse, at 51 days and 8 months posttransplantation, respectively. All 12 patients initially achieved sustained neutrophil engraftment and complete donor chimerism by day 28. Six patients received donor lymphocyte infusion (DLI) after "rescue" therapy to maintain donor chimerism. At 6 months, 4 patients had complete donor cell engraftment, 4 had 15% to 89% stable donor chimerism, and 3 had developed secondary graft failure. This conditioning regimen was generally well tolerated; 4 of the 12 patients never became neutropenic, and 9 never became thrombocytopenic. Only 1 patient developed graft-versus-host disease (GVHD; grade 1), and none had chronic GVHD. Thus, the regimen that we describe can be used with minimal toxicity to effectively overcome graft failure after myeloablative HSCT in children.
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA. nahmed@bcm.edu
authors.forename: Nabil
authors.initials: N
authors.lastname: Ahmed
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Leung
authors.forename: Howard
authors.initials: H
authors.lastname: Rosenblatt
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
authors.forename: Stephen
authors.initials: S
authors.lastname: Gottschalk
authors.forename: Gary D
authors.initials: GD
authors.lastname: Myers
authors.forename: George
authors.initials: G
authors.lastname: Carrum
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Brenner
authors.forename: Robert A
authors.initials: RA
authors.lastname: Krance
mesh_terms: D000293:Adolescent; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000401:mortality / Q000628:therapy*; D006086:Graft vs Host Disease / Q000401:mortality; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D019520:Living Donors; D017710:Lymphocyte Transfusion; D008297:Male; D008659:Metabolic Diseases / Q000401:mortality / Q000628:therapy; D011446:Prospective Studies; D012189:Retrospective Studies; D016511:Severe Combined Immunodeficiency / Q000401:mortality / Q000628:therapy; D015996:Survival Rate; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine